Patent GB-773566-A (GB)
Title: Di-quaternary ammonium substituted alkanes
IPC: C07D217/10
Filed: 1955-02-16
Abstract: The invention comprises unsymmetrical a ,o -di - (quaternary ammonium) - substituted alkane salts having the general formula: <FORM:0773566/IV(b)/1> wherein n is an integer from 3 to 12 inclusive and R and R1 are lower alkyl radicals which may be alike or different or R and R1 may be joined together to form a heterocyclic ring and R11 is a lower alkyl or aralkyl radical or the group -NRR1R11 constitutes an unsaturated or saturated heterocyclic ring and wherein the unsaturated valency is attached to the ring nitrogen atom of a benzopyridine, benzohydropyridine or a benz-substituted benzopyridine or benzohydropyridine such as for example quinoline, isoquinoline or a phenanthridine or a di- or tetra-hydro-quinoline, isoquinoline or phenanthridine and wherein A and A1 are non-toxic anions at least one of which is chlorine, bromine or iodine.  Such compounds are obtained by reacting an o -haloalkyl quaternary ammonium halide of the formula: X-CnH2n-NRR1R11.A-wherein X is chlorine, bromine or iodine with a benzopyridine, benzohydropyridine or a benzsubstituted benzopyridine or benzohydropyridine.  In examples: (1) isoquinoline and 6-bromohexyltrimethyl ammonium bromide are reacted in acetonitrile to give 1-(isoquinolinium)-6 - trimethylammonium) - hexane dibromide.  Similarly prepared are (2) 1-(isoquinolinium)-3-(trimethylammonium) - propane dibromide; (3) 1 - (isoquinolinium) - 3 - (N - methylpyrrolidinium) - propane dibromide; (4) 1 - (isoquinolinium) - 3 - (N - methylmorpholinium) - propane dibromide; (5) 1 - (isoquino - linium) -3-(pyridinium)-propane dibromide; (6) 1 - (4 - acetamidoisoquinolinium) - 3 - (N - methylpyrrolidinium) - propane dibromide; (7) 1 - (methyl - 1,2,3,4 - tetrahydroisoquinolinium) - 3 - (trimethylammonium) - propane dibromide; (8) 1 - (7 - hydroxyquinolinium)-3 - (trimethylammonium) - propane dibromide; (9) 1 - (8 - methoxyquinolinium) - 3 - (trimethylammonium) - propane dibromide; (10) 1-(phenanthridinium) - 3 - (N - methylpyrrolidinium) - propane dibromide; (11) 1-(benzo - [f] - quinolinium) - 3 - (N - methylpyrrolidinium) - propane dibromide; (12) 2-(dimethylaminopropyl) - 2,3 - dihydro - 1 - benzo-[de]-isoquinoline dimethiodide.  A list is given of similarly prepared propane, butane and pentane derivatives in which the 1-substituents are variously isoquinolinium, 4-bromoisoquinolinium, 3 - methyl - isoquinolinium, quinolinium, 8 - hydroxyquinolinium and phenanthridinium radicals.  A further list is given of additional compounds of the above general formula containing quaternary radicals derived also from 1-carbethoxyisoquinoline, 1-methylisoquinoline, 6,7-dimethoxyisoquinoline, 2-butyl - 1,2,3,4 - tetrahydroisoquinoline, 1 - (5-methyl - 5,6 - dihydrophenanthridine, 4-methyl - 1,2,3,4 - tetrahydrobenzo[f]quinoline, benzo[h]quinoline, benz[de]isoquinoline and 2,3-dihydro-benz[de]isoquinoline. Derivatives of benzohydropyridines can be obtained by (a) reaction of naphthalic anhydride with the amine RR1N-CnH2n-NH2; or (b) reaction of a metal salt of naphthalamide with a tertiary aminoalkyl halide RR1-CnH2nX, in each case followed by reduction with lithium aluminium hydride.  Thus, naphthalic anhydride and dimethylaminopropylamine are reacted to give N-dimethylaminopropyl-1,8-naphthalamide (also converted to its hydrochloride and dimethiodide) which is reduced with lithium aluminium hydride to 2-(3-dimethylaminopropyl)-2,3-dihydro-I-benzo-[de]-isoquinoline.